Cardiovascular disease remains the leading cause of mortality of both women and women in the United States, so the health benefits gained from a better understanding of the mechanisms of cardioprotection could be enormous. Considerable epidemiological data indicates that moderate alcohol consumption decreases both the incidence of cardiovascular disease and the mortality associated with myocardial infarction. The cardioprotection associated with moderate alcohol consumption is analogous in many ways to late phase pre-conditioning indicating that they may share common, but yet undefined, molecular mechanisms. The cardiovascular protective effects of alcohol can be categorized into two major responses, (1) effects on systemic circulatory components (blood vessels and blood components), (2) effects on myocardium. This proposal will focus on delineating the mechanisms of the cardio-protective effects of alcohol on the vasculature. Preliminary data show that (1) moderate alcohol enhances vascular function, a form of cardioprotection; (2) moderate alcohol results in induction of nitric oxide synthases (NOS) in the vasculature; (3) induction of NOS involves two isoforms, iNOS and eNOS; (4) bioavailability of .NO may also be increased by induction of superoxide dismutases (SOD); (5) increased bioavailability of .NO may be responsibl4e for the cardiovascular protection associated with moderate alcohol consumption. These data have led to the hypothesis that increased nitric oxide (NO) bioavailability is a critical event in the vascular and cardioprotective events associated with chronic moderate alcohol. This hypothesis will be tested by completion of the following Specific Aims: (1) the vascular protective events associated with chronic moderate ethanol are due to the increased bioavailability of .NO resulting from induction of nitric oxide synthases and increased production of .NO and (2) the vascular protective events associated with chronic moderate ethanol are due to the increased bioavailability of .NO resulting from increased superoxide dismutase and a consequent decrease in superoxide (O2). The information gained from the accomplishment of these specific aims will provide insights into the mechanism which lead to increased .NO-dependent mechanisms in alcohol-induced cardiovascular protection.